The role of cardiac output, blood volume and peripheral resistance in hemorrhagic shock has been well studied. Changes in the extracellular and intracellular fluid volumes, invoked by hemorrhagic shock, have received relatively little attention. Reports from the laboratory here have described a method of simultaneous measurement of plasma volume, extracellular fluid volume and red cells mass in splenectomized animals and in man. This method consists of the use of sulfur-35-labeled sodium sulphate, for extracellular fluid volume, I131-labeled serum albumin for plasma volume, and chromium-51-tagged red blood cells for red blood cell mass. These isotopes are injected simultaneously by the intravenous route. By the use of the combination of energy-differentiating counting instruments, all three isotopes can be determined in any sample after equilibration. A marked disparate reduction of functional extracellular fluid can be demonstrated during hemorrhagic shock in both splenectomized dogs and man. This reduction has been confirmed by the use of other techniques such as inulin. Alleviation of extracellular fluid deficity by the usual balanced salt solution results in a lowering of mortality of a standard irreversible shock preparation, when the balanced salt solution is given prior to the return of shed whole blood. This reduction would appear to be an isotonic intemal redistribution or translocation of extracellular fluid into the intracellular compartment. This reduction appears to be a physiologically important factor in hemorrhagic shock. The nature of this redistribution of functional ECF is under active investigation. Some indirect evidence suggests that the intracellular redistribution may be a translocation from extra-to-intra-cellular fluid in an isotonic fashion. In an attempt to ascertain the possibility of intracellular movement of isotonic extracellular fluid, several avenues of approach are being used, including measurement of cell membrane potential by intracellular microelectrodes.